We have both old and more recent data which indicate that adults at high risk for HIV infection may sometimes become transiently infected with HIV. This includes: (1) transient appearance of serum antibodies (Ab) to conformational epitopes to gp41/gp160;(2) transient appearance of HIV in the PBMCs at the same time as Ab in some of the cases;(3) paternity typing of PBMC samples taken at the time of Ab and virus positivity, and later, when the subject is negative for both, thereby showing that they are from the same subject;(4) sequence analysis of the viruses present in transiently infected subjects, showing that they are not lab contaminants;and (5) demonstration in one case in which the virus in a transiently infected subject was genetically related to the virus in genital fluids from his HIV+ partner. Longitudinal statistics from studies of 37 high-risk subjects over 4 years showed that putative transient infections were more frequent than progressive infections and that the former was associated with unprotected oral sex, while the later was associated with unprotected genital sex. HIV was found by PCR in the tonsil of one such transiently HIV infected subject, but it was not detected in the PBMCs. We hypothesize that transient HIV infections do occur in high-risk adults, and we will focus this project only on proving or disproving this hypothesis. Our specific aims iare 1) to longitudinally screen at every 2-3 months 300 high-risk subjects for serological evidence of HIV infection;(2) attempt to detect HIV in the Ab-positive subjects and their source partners by nested PCR and PBMC culture;(3) sequence env and nef genes that are amplified and perform phylogenetic analyses to show relatedness between viruses in putative transiently infected subjects and their source partners;and (4) demonstrate that blood samples have not been mixed up. Although transient infection is presently controversial, our data indicate that it occurs and we will attempt to prove it.